Childhood obesity is a formidable health threat, with 1 in 3 American children overweight or obese. Innovative approaches are needed to reverse this epidemic and prevent related complications such as type 2 diabetes and high blood pressure. Deficiency of Vitamin D, a fat-soluble hormone, may be a novel modifiable risk factor in the development of obesity and related sequelae. The vitamin D receptor and the enzyme 25-OH vitamin D-11-hydroxylase, which converts vitamin D to its active form, are expressed by many body tissues with key metabolic roles in the development of obesity and related conditions. Epidemiologic data in adults suggest that vitamin D deficiency is related to obesity, type 2 diabetes, and hypertension. Recent animal and human data have raised the possibility that vitamin D and components of its metabolic pathway may be associated with modulation of intrauterine and postnatal growth, body weight, insulin sensitivity and blood pressure. Further, maternal vitamin D status during pregnancy is associated with chronic disease in offspring, and the prenatal period has been implicated as a critical window for obesity development. Despite these promising findings, little data exist regarding the potential impact of maternal-fetal vitamin D status on the development of child obesity and related metabolic conditions. The goals of this study are to examine the extent to which maternal and fetal vitamin D status are associated with the development of childhood adiposity, insulin resistance, and blood pressure. We will determine the extent to which 1) maternal and cord blood 25-OH vitamin D levels, and 2) single nucleotide polymorphisms in child vitamin D receptor (VDR) and other genes that affect vitamin D metabolism or signaling, are associated with child adiposity, insulin resistance, and blood pressure at ages 3 and 7 years. We will carry out study aims within Project Viva, a longitudinal pre-birth cohort study of 1300 U.S. women enrolled during pregnancy, and their offspring. Project Viva was specifically designed to examine the effects of pre- and postnatal factors on child health outcomes. Data collected include detailed information about maternal and child diet, and sociocultural variables;stored blood from pregnancy and delivery;and adiposity-related outcome measures at ages 3 and 7 years, including DXA, blood pressure, and stored blood for hormonal assays. By using a pre-existing database, this proposal offers an efficient, cost-effective means to test novel hypotheses. Our findings may lead to new scientific insights about early postnatal pathways leading to obesity. Furthermore, the study results could have important public health implications. If lower maternal-fetal vitamin D status in early life is associated with greater adiposity, insulin resistance and higher blood pressure in childhood, our findings could inform dietary recommendations during pregnancy designed to reduce the incidence of obesity in future generations. PUBLIC HEALTH RELEVANCE: Project Narrative The proposed investigation of the relationship between maternal-fetal vitamin D status and child adiposity, insulin resistance and blood pressure has important public health implications. If we confirm that deficient maternal-fetal vitamin D status is related to childhood obesity, insulin resistance, and blood pressure, this knowledge could lead to public health initiatives directed at increasing maternal vitamin D intake during pregnancy. In turn, such initiatives could substantially reduce the rates of obesity and related metabolic conditions in future generations.